Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham , Birmingham, Alabama.
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham , Birmingham, Alabama.
Am J Physiol Heart Circ Physiol. 2018 Feb 1;314(2):H278-H284. doi: 10.1152/ajpheart.00471.2017. Epub 2017 Nov 3.
Vascular endothelial growth factor (VEGF) is a well-characterized proangiogenic cytokine that has been shown to promote neovascularization in hearts of patients with ischemic heart disease but can also lead to adverse effects depending on the dose and mode of delivery. We investigated whether prolonged exposure to a low dose of VEGF could be achieved by encapsulating VEGF in polylactic coglycolic acid nanoparticles and whether treatment with VEGF-containing nanoparticles improved cardiac function and protected against left ventricular remodeling in the hearts of mice with experimentally induced myocardial infarction. Polylactic coglycolic acid nanoparticles with a mean diameter of ~113 nm were generated via double emulsion and loaded with VEGF; the encapsulation efficiency was 53.5 ± 1.7% (107.1 ± 3.3 ng VEGF/mg nanoparticles). In culture, VEGF nanoparticles released VEGF continuously for at least 31 days, and in a murine myocardial infarction model, VEGF nanoparticle administration was associated with significantly greater vascular density in the peri-infarct region, reductions in infarct size, and improvements in left ventricular contractile function 4 wk after treatment. Thus, our study provides proof of principle that nanoparticle-mediated delivery increases the angiogenic and therapeutic potency of VEGF for the treatment of ischemic heart disease. NEW & NOTEWORTHY Vascular endothelial growth factor (VEGF) is a well-characterized proangiogenic cytokine but has a short half-life and a rapid clearance rate. When encapsulated in nanoparticles, VEGF was released for 31 days and improved left ventricular function in infarcted mouse hearts. These observations indicate that our new platform increases the therapeutic potency of VEGF.
血管内皮生长因子（VEGF）是一种特征明确的促血管生成细胞因子，已被证明可促进缺血性心脏病患者的新血管生成，但根据剂量和给药方式的不同，也可能产生不良反应。我们研究了通过将 VEGF 包封在聚乳酸-羟基乙酸共聚物纳米粒子中是否可以实现长时间低剂量暴露，以及用含 VEGF 的纳米粒子治疗是否可以改善实验性心肌梗死小鼠的心脏功能并防止左心室重构。通过双乳液法生成平均直径约为 113nm 的聚乳酸-羟基乙酸共聚物纳米粒子，并负载 VEGF；包封效率为 53.5±1.7%（107.1±3.3ng VEGF/mg 纳米粒子）。在培养中，VEGF 纳米粒子至少持续 31 天释放 VEGF，在小鼠心肌梗死模型中，VEGF 纳米粒子给药与梗死周围区域血管密度显著增加、梗死面积减少以及治疗 4 周后左心室收缩功能改善相关。因此，我们的研究提供了一个原理性证明，即纳米颗粒介导的递送可增加 VEGF 的血管生成和治疗效力，用于治疗缺血性心脏病。 新观点和值得注意的地方 血管内皮生长因子（VEGF）是一种特征明确的促血管生成细胞因子，但半衰期短，清除率快。包封在纳米粒子中时，VEGF 可释放 31 天，并改善梗死小鼠心脏的左心室功能。这些观察结果表明，我们的新平台增加了 VEGF 的治疗效力。
